On the laboratory scale, it has already been a good ten years since direct communication between nerve cells and electrically active solid-state structures, such as e.g. semiconductors, left the realm of fiction. Successful laboratory experiments have been reported for example by P. Fromherz et al. in Science 252, 1290 (1991); P. Fromherz et al. in Physical Review Letters 75, 1670 (1995) and also P. Stett et al. in Physical Review E Vol. 55, No. 2, 1779 (1997). A summary overview of the early results is given by P. Fromherz in Berichte der Bunsen Gesellschaft No. 7, 1093 (1996). Furthermore, first biochips produced on industrial scales have recently been presented. Modern biochips are thus opening up a wide variety of fields of use from neurobiological fundamental research through to high-throughput screening applications in the pharmaceutical industry.
A basic element of such modern biochips is illustrated schematically in FIG. 5(a). The biochip comprises a carrier structure 10, which may comprise for example a patterned semiconductor substrate (semiconductor structure). The carrier structure 10 is separated from an electrolyte 14 by a dielectric layer 12. The corresponding equivalent circuit diagram is illustrated in FIG. 5(b). Generally, in an electrolyte, the electrically communicating nerve cells are cultivated directly at those locations on the surface of the carrier structure 10 where the active locations of electrical stimulation and detection devices are situated.
Whereas the electrical activity is carried by ions in biological systems, electrons or holes are responsible for charge transport in semiconductors. Therefore, in a manner corresponding to the natural boundary layer between electrolyte 14 and semiconductor structure, a capacitive coupling is preferably utilized both during the stimulation and during the detection of biological processes. This currentless mechanism of electrical coupling between the biochip and the nerve cell to be stimulated or to be detected is based on the principle of electrical induction (electrostatic induction, also called influence). The electrical coupling is brought about by the fact that an accumulation of charge in the nerve cell induces corresponding mirror charges in the biochip, the effect of which for example on the electrical transport properties of the carrier structure 10 designed as a semiconductor structure can be demonstrated.
Conversely, nerve cells arranged at the dielectric layer 12 of the carrier or semiconductor structure 10 can be stimulated by virtue of the fact that an accumulation of charge in a stimulation device of the semiconductor structure 10 induces charges in the nerve cell. The dielectric layer 12 between the semiconductor structure 10 and the electrolyte 14 is accorded a particular importance in the case of such a biochip which utilizes a capacitive coupling to the nerve cell to be examined both during stimulation processes and during detection processes.
Conventionally, silicon-based, active and thus CMOS-enabled semiconductor structures are coated with SiO2 in order to form such a dielectric boundary or surface layer 12. It has been shown, however, that, in particular with regard to the coupling efficiency or the achievable signal transfer between stimulation and/or sensor device of the biochip and the biological tissues being examined, a dielectric layer made of SiO2 yields results that are satisfactory only to a limited extent.